Intestinal Permeability, aka "Leaky Gut", and the Microbiome
The impacts of intestinal permeability. The role of the gut microbiome on intestinal permeability, and how to detect and modulate "leaky gut".
General:
Review, Feb 2022: Gut barrier disruption and chronic disease https://www.sciencedirect.com/science/article/abs/pii/S1043276022000029
Review, Feb 2019: Cellular and Molecular Therapeutic Targets in Inflammatory Bowel Disease—Focusing on Intestinal Barrier Function https://www.mdpi.com/2073-4409/8/2/193/htm
Review, 2017: "Leaky Gut" section: http://www.tandfonline.com/doi/full/10.1080/19490976.2017.1293224 "bacteria may enter the body by endocytosis, which has been observed in the absence of tight junctional damage. Data in various disease states support the hypothesis of microbiota translocation to the blood stream"
Mucus organisation is shaped by colonic content; a new view (2017): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561085/ "Our findings reopen the discussion on the nature of the colonic mucus barrier"
Review, 2013: Zonulin, regulation of tight junctions, and autoimmune diseases: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3384703/
Review, 2008: Physiological, Pathological, and Therapeutic Implications of Zonulin-Mediated Intestinal Barrier Modulation: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570116/
"Of note, the organisms that were present in the liver and spleen in LE mice, Enterobacter and Enterococcus, matched those that were increased in the intestine, implying that the intestine is the source of bacterial invasion" (Jul 2020, sepsis) https://www.nature.com/articles/s41598-020-69797-z
Antibodies Set Boundaries Limiting Microbial Metabolite Penetration and the Resultant Mammalian Host Response (2018): https://doi.org/10.1016/j.immuni.2018.08.004
The study demonstrated that loss of TET2 [gene] expression leads to defects in the intestinal barrier, allowing bacteria living in the gut to spread into the blood and peripheral organs (2018): https://medicalxpress.com/news/2018-05-conditions-bacterial-stage-leukemia.html
Commensal microbiota induces colonic barrier structure and functions that contribute to homeostasis (2018): https://doi.org/10.1038/s41598-018-32366-6 "In conclusion, commensal colonization promotes physiological barrier structural and functional adaptations that contribute to intestinal homeostasis. These findings indicate that the presence of commensal microbiota impacts colonic ultrastructure, Tight junction (TJ) proteins and paracellular permeability."
Normal Intestinal Microbiome Enhances Intestinal Barrier. Enhancement of the gut barrier integrity by a microbial metabolite (Urolithin A) through the Nrf2 pathway (Jan 2019) https://web.archive.org/web/20201107225750/https://medicalresearch.com/author-interviews/normal-intestinal-microbiome-enhances-intestinal-barrier/46888/
In diseases:
Researchers find increased intestinal permeability is precursor of celiac disease in pediatric study (Dec 2023, n=103) https://medicalxpress.com/news/2023-12-intestinal-permeability-precursor-celiac-disease.html Zonulin as a Biomarker for the Development of Celiac Disease.
"Parkinson’s Disease patients exhibit a pro-inflammatory microbiota profile in their intestinal tract that might increase gut permeability, allowing leakage of bacterial products and inflammatory mediators from the intestines" (2017): https://link.springer.com/article/10.1007%2Fs40473-017-0129-2
Intestinal barrier disruption and dysregulated mucosal immunity contribute to kidney fibrosis in chronic kidney disease (2018): https://academic.oup.com/ndt/advance-article-abstract/doi/10.1093/ndt/gfy172/5043141
Severe Defects in the Macrophage Barrier to Gut Microflora in Inflammatory Bowel Disease and Colon Cancer (2018): http://ar.iiarjournals.org/content/38/7/3811
Autoimmunity-Associated Gut Commensals Modulate Gut Permeability and Immunity in Humanized Mice (Mar, 2019): https://doi.org/10.1093/milmed/usy309
Elevated fecal calprotectin in patients with Alzheimer’s dementia indicates leaky gut (2015): https://link.springer.com/article/10.1007%2Fs00702-015-1381-9
Modulation:
Fecal microbiota transplantation ameliorates abdominal obesity through inhibiting microbiota-mediated intestinal barrier damage and inflammation in mice (Feb 2024) https://www.sciencedirect.com/science/article/abs/pii/S0944501324000557
Washed microbiota transplantation improves symptoms and intestinal barrier function in patients with functional bowel disorders: a propensity-score matching analysis (Jan 2024, n=68) https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-024-03131-z
Fecal microbiota transplantation repairs intestinal permeability and regulates the expression of 5-HT to influence alcohol-induced depression-like behaviors in C57BL/6J mice (Jan 2024) https://www.frontiersin.org/articles/10.3389/fmicb.2023.1241309/full
Fecal Microbiota Transplantation Beneficially Regulates Intestinal Mucosal Autophagy and Alleviates Gut Barrier Injury (2018): https://doi.org/10.1128/mSystems.00137-18
Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions (2018): https://www.nature.com/articles/emm2017282
Examine's list: https://examine.com/topics/intestinal-permeability/
Just Thrive Bacillus spores reduce signs of leaky gut: https://thriveprobiotic.com/blogs/blog/groundbreaking-study-on-healing-leaky-gut-with-the-strains-used-in-just-thrive-probiotic - https://www.wjgnet.com/2150-5330/full/v8/i3/117.htm
Apple Polysaccharide inhibits microbial dysbiosis and chronic inflammation and modulates gut permeability in HFD-fed rats: http://www.sciencedirect.com/science/article/pii/S0141813016314842
"identifies a mechanism through which intestinal bacteria such as Lactobacillus strengthen the intestinal barrier to support a mutually beneficial relationship and prevent inflammation" https://medicalxpress.com/news/2019-01-scientists-watchdog-intestinal-bacteria.html. Microbiota Sensing by Mincle-Syk Axis in Dendritic Cells Regulates Interleukin-17 and -22 Production and Promotes Intestinal Barrier Integrity (2019): https://doi.org/10.1016/j.immuni.2018.12.020
Bifidobacterium dentium Fortifies the Intestinal Mucus Layer via Autophagy and Calcium Signaling Pathways (June 2019): https://mbio.asm.org/content/10/3/e01087-19
Bacterial butyrate prevents atherosclerosis by maintaining gut barrier function in mice. Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model (Nov 2018) https://www.gutmicrobiotaforhealth.com/en/bacterial-butyrate-prevents-atherosclerosis-by-maintaining-gut-barrier-function-in-mice/
Drugs that significantly altered gut microbial composition did not increase intestinal permeability, suggesting that the two factors are not causally linked (2018): https://doi.org/10.1007/s00213-018-5006-5
Increase:
N-acetyl cysteine (NAC) increases permeability: https://www.ncbi.nlm.nih.gov/pubmed/8950741 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261620/
Soy lecithin increases intestinal permeability to proinflammatory endotoxins: https://www.ocl-journal.org/articles/ocl/pdf/2016/03/ocl160009-s.pdf
Gliadin (a component of gluten) activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules (2006): https://doi.org/10.1080/00365520500235334
"switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related (functional gastrointestinal disorder) symptoms and decreased small intestinal microbial diversity while increasing small intestinal permeability" (May 2019): https://www.nature.com/articles/s41467-019-09964-7
Diagnostics:
Review, Aug 2020: The Intestinal Barrier and Current Techniques for the Assessment of Gut Permeability https://www.mdpi.com/2073-4409/9/8/1909
Inflammatory bowel disease associates with increased gut‐to‐blood penetration of SCFA: A new, noninvasive marker of a functional intestinal lesion (June 2019) https://newatlas.com/gut-bowel-disease-detection-bowel-ibd-ibs-celiac/60390/ - https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/EP087773
Dr. Zsófia Clemens covers permeability, including the various tests (2019): https://www.youtube.com/watch?v=nDPM8o9jcFA?t=400
GI Effects stool test have a test for zonulin: https://www.gdx.net/core/sample-reports/gi-effects-2200-sample-report.pdf - "Zonulin is a protein modulator of intestinal tight junctions and is used to assess intestinal permeability. It can be used for assessing impaired gut barrier function for various conditions"
Serum zonulin testing isn't accurate/useful (Jan 2019): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331146/
"The idea of zonulin being a factor of concern has primarily been put forth by one researcher, Alessio Fasano, who happens to sell a book called Gluten Freedom. There haven't been any RCT trials regarding different diets and serum zonulin" https://archive.fo/jLvgD#selection-3227.10-3227.11